Sitaxsentan sodium

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种强效、长效、口服活性、选择性 ETA 受体拮抗剂，可与人 ETA 受体竞争性结合，Ki 为 0.43 nM，IC50 为 1.4 nM。

A potent, long acting, orally active, selective ETA receptor antagonist that binds competitively to human ETA receptor with Ki of 0.43 nM, IC50 of 1.4 nM; dispalys >5,000-fold selectivity over ETB receptors; inhibits ET1-induced stimulation of phosphoinositide turnover with Ki of 0.686 nM, and pA2 of 8.0; excellent PK profile and oral bioavailability.Hypertension Withdrawn(In Vitro):Sitaxsentan and Bosentan attenuate NTCP transport at higher concentrations, and inhibit human hepatic transporters, which provides a potential mechanism for the increased hepatotoxicity observed for these agents in the clinical setting. Only sitaxsentan decreased OATP transport (52%). Sitaxsentan and sitaxsentan combined with sildenafil completely prevent the increased expressions of endothelin-1 and of the ETB receptor. Sitaxsentan alone partially restores the expressions of BMPR-1A and BMPR-2. The combination of sildenafil and sitaxsentan further restores the expressions of BMPR-1A and BMPR-2, which remaines, however, decreased compared with controls.(In Vivo):Sitaxsentan (5 mg/kg infused iv 10 min prior to onset of hypoxia) completely blocks hypoxia-induced vasoconstriction and this group does not differ from air controls. Oral administration of sitaxsentan, significantly attenuates the increase in MPAP, while the administration of sitaxsentan to rats exposed to normal oxygen levels is without effect on MPAP. Sitaxsentan alone limits shunt-induced increase in MT. Sitaxsentan combined with sildenafil more effectively prevents this remodeling, which, however, tends to remain increased compared with controls.

Sitaxsentan and Bosentan attenuate NTCP transport at higher concentrations, and inhibit human hepatic transporters, which provides a potential mechanism for the increased hepatotoxicity observed for these agents in the clinical setting. Only sitaxsentan decreased OATP transport (52%). Sitaxsentan and sitaxsentan combined with sildenafil completely prevent the increased expressions of endothelin-1 and of the ETB receptor. Sitaxsentan alone partially restores the expressions of BMPR-1A and BMPR-2. The combination of sildenafil and sitaxsentan further restores the expressions of BMPR-1A and BMPR-2, which remaines, however, decreased compared with controls.

Sitaxsentan (5 mg/kg infused iv 10 min prior to onset of hypoxia) completely blocks hypoxia-induced vasoconstriction and this group does not differ from air controls. Oral administration of sitaxsentan, significantly attenuates the increase in MPAP, while the administration of sitaxsentan to rats exposed to normal oxygen levels is without effect on MPAP. Sitaxsentan alone limits shunt-induced increase in MT. Sitaxsentan combined with sildenafil more effectively prevents this remodeling, which, however, tends to remain increased compared with controls.

TBC-11251 sodium | TBC-11251

GPCR/G Protein

Endothelin Receptor

ET-A

Cardiovascular Disease

Hypertension

210421-74-2

476.8863

C18H14ClN2NaO6S2

>98% (HPLC)

10 mM in DMSO

CC1=CC2=C(C=C1CC(=O)C3=C(C=CS3)S(=O)(=O)[N-]C4=C(C(=NO4)C)Cl)OCO2.[Na+]

3-Thiophenesulfonamide, N-(4-chloro-3-methyl-5-isoxazolyl)-2-[2-(6-methyl-1,3-benzodioxol-5-yl)acetyl]-, sodium salt (1:1)

(-20℃)

With Ice Pack

≥ 2 years